Symptoms Lyme disease is the most common tick-borne infection in North America. Although the outcome after treatment is generally excellent, some patients complain of persistent subjective symptoms such as fatigue, musculoskeletal pains, or problems with concentration and memory despite resolution of the objective signs of the disease. However, these symptoms are also common in the general population and a causal association between Lyme disease and persistent symptoms has not been established. An unanswered and critically important question is whether, after treatment for Lyme disease, patients are more likely to have chronic (>6 months) subjective symptoms than are individuals who did not have Lyme disease. To answer this fundamental question, we propose to conduct the first prospective, controlled longitudinal cohort study in the United States in which subjects with and without Lyme disease are carefully evaluated in a similar manner for a full year. This study will also be the first to be able to determine the incidence of post-Lyme disease syndrome (PLDS) and the associated medical complications and economic costs. We will also obtain a blood sample from such patients to be shared with other investigators for future research on possible biomarkers associated with PLDS. Finally, in a different cohort of patients, we will describe for the first time the outcome of culture-confirmed patients with early Lyme disease more than 10 years after diagnosis and treatment. PUBLIC HEALTH RELEVANCE: The purpose of our study is to determine whether patients treated for Lyme disease are more likely to have persistent symptoms than individuals who did not have Lyme disease. To answer this fundamental and previously unanswered question, we propose to conduct the first prospective study in the United States in which subjects with and without Lyme disease are carefully evaluated in a similar manner for a full year. In a different group of patients, we will describe for the first time the outcome of patients with early Lyme disease more than 10 years after diagnosis and treatment.